DESCRIPTION (taken from the application) Our understanding of the regulation of energy balance, and defects in this system that result in obesity, has undergone dramatic progress in recent years. Insights gained from identifying the genetic basis of several monogenic obesities in rodents and humans have allowed us to define the existence of a novel regulated physiologic system by which the status of energy balance and energy stores in peripheral tissues is communicated to central nervous system circuits that regulate hunger, energy expenditure and neuroendocrine function. Critical areas of recent discovery involve the adipocyte hormone leptin, the mechanism for leptin signaling and action both within and outside the CNS, identification of a coordinated group of leptin target neurons in the hypothalamus, including the melanocortin pathway that involves antagonistic ligands and several receptors, mapping of downstream targets in the CNS, and elucidation of effector pathways, including those that influence energy expenditure by regulating mitochondrial coupling. The goal of this Keystone Symposium is to bring together investigators from diverse aspects of this field, including neurobiologists, geneticists, physiologists and pharmacologists to integrate and provide new directions for this rapidly moving field.